@article{0d48713b09b4473098fff23bf5d80e9f,
title = "Polygenic risk scores point toward potential genetic mechanisms of type 2 myocardial infarction in people with HIV",
abstract = "Background: People with human immunodeficiency virus (HIV) infection (PWH) are at higher risk of myocardial infarction (MI) than those without HIV. About half of MIs in PWH are type 2 (T2MI), resulting from mismatch between myocardial oxygen supply and demand, in contrast to type 1 MI (T1MI), which is due to primary plaque rupture or coronary thrombosis. Despite worse survival and rising incidence in the general population, evidence-based treatment recommendations for T2MI are lacking. We used polygenic risk scores (PRS) to explore genetic mechanisms of T2MI compared to T1MI in PWH. Methods: We derived 115 PRS for MI-related traits in 9541 PWH enrolled in the Centers for AIDS Research Network of Integrated Clinical Systems cohort with adjudicated T1MI and T2MI. We applied multivariate logistic regression analyses to determine the association with T1MI and T2MI. Based on initial findings, we performed gene set enrichment analysis of the top variants composing PRS associated with T2MI. Results: We found that T1MI was strongly associated with PRS for cardiovascular disease, lipid profiles, and metabolic traits. In contrast, PRS for alcohol dependence and cholecystitis, significantly enriched in energy metabolism pathways, were predictive of T2MI risk. The association remained after the adjustment for actual alcohol consumption. Conclusions: We demonstrate distinct genetic traits associated with T1MI and T2MI among PWH further highlighting their etiological differences and supporting the role of energy regulation in T2MI pathogenesis.",
keywords = "Energy metabolism, HIV, Polygenic risk score, Type 1 myocardial infarction, Type 2 myocardial infarction",
author = "Lee, {Won Jun} and Haoxiang Cheng and Whitney, {Bridget M.} and Nance, {Robin M.} and Britton, {Sierra R.} and Kristina Jordahl and Sara Lindstrom and Ruderman, {Stephanie A.} and Kitahata, {Mari M.} and Saag, {Michael S.} and Willig, {Amanda L.} and Greer Burkholder and Eron, {Joseph J.} and Kovacic, {Jason C.} and Bj{\"o}rkegren, {Johan L.M.} and Mathews, {W. Christopher} and Edward Cachay and Feinstein, {Matthew J.} and Mathew Budoff and Hunt, {Peter W.} and Moore, {Richard D.} and Jeanne Keruly and McCaul, {Mary E.} and Geetanjali Chander and Allison Webel and Mayer, {Kenneth H.} and Delaney, {Joseph A.} and Crane, {Paul K.} and Claudia Martinez and Crane, {Heidi M.} and Ke Hao and Inga Peter",
note = "Funding Information: This work was supported by the National Heart, Lung, And Blood Institute [ R01HL125027 to IP and HMC; R01 HL126538 to JD; R01 HL156792 to MJF], National Human Genome Research Institute [ R01HG010649 to IP and HMC], National Institute on Drug Abuse [ R01DA047045 to HMC and IP; U01DA03693 to RDM and JCK], National Institute on Alcohol Abuse and Alcoholism [ U24AA020801 to MEC and GC]. Additional support came from the National Institute of Allergy and Infectious Diseases [ R24AI067039 , P30AI027757 and P30AI027767 to MSS; P30AI094189 to RDM], National Institute of Environmental Health Sciences [ R01ES029212 to KH]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Funding Information: This work was supported by the National Heart, Lung, And Blood Institute [R01HL125027 to IP and HMC; R01 HL126538 to JD; R01 HL156792 to MJF], National Human Genome Research Institute [R01HG010649 to IP and HMC], National Institute on Drug Abuse [R01DA047045 to HMC and IP; U01DA03693 to RDM and JCK], National Institute on Alcohol Abuse and Alcoholism [U24AA020801 to MEC and GC]. Additional support came from the National Institute of Allergy and Infectious Diseases [R24AI067039, P30AI027757 and P30AI027767 to MSS; P30AI094189 to RDM], National Institute of Environmental Health Sciences [R01ES029212 to KH]. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Publisher Copyright: {\textcopyright} 2023 The Author(s)",
year = "2023",
month = jul,
day = "15",
doi = "10.1016/j.ijcard.2023.04.058",
language = "English",
volume = "383",
pages = "15--23",
journal = "International Journal of Cardiology",
issn = "0167-5273",
publisher = "Elsevier",
}
